title: Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor.
abstract: Tumor cells can activate platelets, which in turn facilitate tumor cell survival and dissemination. The exact mechanisms by which platelets promote metastasis have remained unclear. Here, we show that adenine nucleotides released from tumor cell-activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and thereby promote cancer cell extravasation. We identified the endothelial P2Y2 receptor, which is activated by ATP, as the primary mediator of this effect. Mice deficient in P2Y2 or lacking ATP secretion from platelets show strongly reduced tumor cell metastasis. These findings demonstrate a mechanism by which platelets promote cancer cell metastasis and suggest the P2Y2 receptor and its endothelial downstream signaling mechanisms as a target for antimetastatic therapies.
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, 61231 Bad Nauheim, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Schumacher
authors.forename: Boris
authors.initials: B
authors.lastname: Strilic
authors.forename: Kishor Kumar
authors.initials: KK
authors.lastname: Sivaraj
authors.forename: Nina
authors.initials: N
authors.lastname: Wettschureck
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002465:Cell Movement; D003594:Cytoplasmic Granules / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D058473:Receptors, Purinergic P2Y2 / Q000502:physiology*
chemical_list: D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate